This page shows what was measured, who it was measured in, and what that does not settle.
What 3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE does in the body
The same molecule also slows a potassium current in heart muscle, which stretches out the time the heart takes to reset between beats.
Ziprasidone blocks the dopamine receptor that antipsychotics have targeted since the 1950s and blocks several serotonin receptors at the same time, and it also weakly does what an antidepressant does by slowing the reuptake of serotonin and noradrenaline. It barely touches the receptors that drive appetite, which is why it is one of the few drugs in this class that does not reliably put weight on. It has to be swallowed with food, because on an empty stomach the body absorbs about half as much.
Why people take it. Schizophrenia, and the manic phase of bipolar disorder
What happened in people
A standardised mean difference of 0.39 against placebo for overall symptom change, eleventh of fifteen ranked antipsychotics
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
An intramuscular form for acute agitation, made possible only by a cyclodextrin that carries the poorly soluble molecule into solution
Where it acts
Mesolimbic and mesocortical dopamine synapses, and the cardiac hERG potassium channel, where the same molecule slows the electrical recovery of the ventricle
Kind of result
Symptoms and quality of life
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
Its recorded molecular formula is C21H21ClN4OS, weighing 412.94.
US prescribing information · 1ffd16c3-25ac-4839-9ea9-4efd32926b95 · read 2026-08-30
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 134 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Non-suicide mortality within one year of initiating ziprasidone or olanzapine, in naturalistic practice across 18 countries
✓ The study showed what it set out to show
Who was studied
NCT00418171 (ZODIAC)
How many people
18154
Study design
Phase 4 open-label randomised post-marketing large simple trial
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Non-suicide mortality 0.91 on ziprasidone against 0.90 on olanzapine; relative risk 1.02 (95% CI 0.76 to 1.39)
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The authors state the study was neither powered nor designed to examine the risk of rare events like torsade de pointes, which is the event the QT warning exists to prevent. Follow-up was by unblinded treating psychiatrists, and sudden death was analysed post hoc.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule taken twice daily with food, and an intramuscular injection for acute agitation in schizophrenia
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
NCT00418171 — ZODIAC, the randomised post-marketing cardiovascular safety trial (NCT00418171) · a recorded source, not a stored snapshot
Time to discontinuation of assigned antipsychotic for any cause in chronic schizophrenia
✗ The study did not show it
Who was studied
NCT00014001 (CATIE, phase 1)
How many people
1493
Study design
Phase 4 double-blind randomised effectiveness trial, up to 18 months
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
79% of ziprasidone patients discontinued before 18 months against 64% on olanzapine, 74% on risperidone, 75% on perphenazine and 82% on quetiapine; olanzapine versus ziprasidone p=0.028, which did not meet the study's adjusted threshold
Repeated elsewhere
Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Ziprasidone entered the trial late, after its approval, so its arm accrued fewer patients than the others. The trial was publicly funded and no drug arm retained a majority of its patients.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule taken twice daily with food, and an intramuscular injection for acute agitation in schizophrenia
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
NCT00418171 — ZODIAC, the randomised post-marketing cardiovascular safety trial (NCT00418171) · a recorded source, not a stored snapshot
Change from baseline in PANSS total score, with ziprasidone as active control
✓ The study showed what it set out to show
Who was studied
NCT00254202
How many people
593
Study design
Randomised double-blind placebo- and active-controlled trial in acute exacerbation
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Mean change -12.3 on ziprasidone and -12.0 on iloperidone against -7.1 on placebo
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The sponsor was Vanda Pharmaceuticals, a competitor with no commercial interest in ziprasidone, which makes this a cleaner estimate of its effect than a manufacturer-run registration trial.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule taken twice daily with food, and an intramuscular injection for acute agitation in schizophrenia
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
NCT00418171 — ZODIAC, the randomised post-marketing cardiovascular safety trial (NCT00418171) · a recorded source, not a stored snapshot
Mean overall change in symptoms against placebo in acute schizophrenia, with all-cause discontinuation, weight gain, extrapyramidal effects, prolactin, QTc and sedation as secondary outcomes
✓ The study showed what it set out to show
Who was studied
Leucht 15-drug multiple-treatments meta-analysis
How many people
43049
Study design
Bayesian network meta-analysis of 212 blinded randomised trials
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Ziprasidone standardised mean difference 0.39 (95% CrI 0.30 to 0.49), eleventh of fifteen
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Ziprasidone sits toward the unfavourable end of the QTc range in the same analysis, in which lurasidone was most favourable at 0.10 and sertindole least at -0.90.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule taken twice daily with food, and an intramuscular injection for acute agitation in schizophrenia
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
NCT00418171 — ZODIAC, the randomised post-marketing cardiovascular safety trial (NCT00418171) · a recorded source, not a stored snapshot
What we know
RNAWiki holds 5 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE
What a person takes: Oral capsule taken twice daily with food, and an intramuscular injection for acute agitation in schizophrenia.
The measurement behind this step
The capsule must be swallowed whole with a meal and must not be opened, crushed or chewed. Fed bioavailability is about 60% and absorption roughly doubles with food, so the meal is part of the dose. The intramuscular form is a sulfobutylether-beta-cyclodextrin complex, a formulation choice forced by the free base being too poorly water-soluble to inject on its own. There is no long-acting injectable.
Getting in
A capsule taken twice a day, always with food
Ziprasidone is a capsule swallowed whole, twice daily, with a meal. Without food the body absorbs about half as much, so a missed meal changes the dose rather than the timing.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Absolute bioavailability of a 20 mg dose under fed conditions is approximately 60%, and absorption is increased up to two-fold in the presence of food. Peak plasma concentration is reached at 6 to 8 hours. Plasma protein binding exceeds 99%, mainly to albumin and alpha-1-acid glycoprotein.
It reaches the brain and is broken down mostly by an enzyme that is not P450
The drug enters the brain and is then cleared, mainly through a pathway that is different from the one most psychiatric drugs use, which keeps its interaction list shorter than expected.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Approximately two-thirds of clearance is by aldehyde oxidase-mediated reduction, with the remainder by CYP3A4 oxidation. Less than 1% is excreted unchanged in urine and under 4% in faeces. The four major circulating metabolites are benzisothiazole sulphoxide and sulphone, ziprasidone sulphoxide and S-methyldihydroziprasidone, and none carries the parent's activity.
It blocks dopamine D2 and serotonin 5-HT2A, and blocks serotonin reuptake too
It switches off the dopamine receptor that dampens hallucinations and delusions, switches off several serotonin receptors, and additionally slows the reuptake of serotonin and noradrenaline in the way an antidepressant does.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Antagonism at D2 (Ki 4.8 nM), D3 (7.2 nM), 5-HT2A (0.4 nM), 5-HT2C (1.3 nM), 5-HT1D (2 nM) and alpha-1 (10 nM), with agonism at 5-HT1A (3.4 nM). The 5-HT2A to D2 ratio of roughly ten to one is among the highest in the class. Synaptic reuptake inhibition of serotonin and noradrenaline is stated in the label and is an unusual property for an antipsychotic.
The same molecule blocks a potassium channel in heart muscle
A potassium channel in heart cells does the work of resetting the electrical charge after each beat. Ziprasidone slows it, and the electrocardiogram records the delay as a longer QT interval.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Block of the hERG-encoded rapid delayed-rectifier potassium current prolongs ventricular repolarisation. In the label's head-to-head study, the mean QTc increase from baseline was approximately 9 to 14 msec greater than risperidone, olanzapine, quetiapine and haloperidol, and approximately 14 msec less than thioridazine. Co-administration with ketoconazole did not augment it, which points to a direct channel effect rather than a metabolic one.
Symptoms fall modestly, weight stays put, the electrocardiogram changes
The effect on symptoms is in the middle of the field. Weight, blood sugar and cholesterol stay largely where they were, which is the main reason to choose it. The trade is on the heart tracing.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Standardised mean difference against placebo of 0.39 (95% CrI 0.30 to 0.49) for overall symptom change, eleventh of fifteen. Weight gain toward the favourable end of the fifteen-drug range. QTc increased by approximately 10 msec at 160 mg daily against placebo. In 18,154 randomised patients, one-year non-suicide mortality was 0.91 against 0.90 for olanzapine, relative risk 1.02 (95% CI 0.76 to 1.39).
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Adults with schizophrenia and bipolar disorder, chosen most often when weight gain and metabolic disturbance are the deciding problem and the person has no cardiac history.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “The safety and effectiveness of Ziprasidone have not been established in pediatric patients.”
US prescribing information · 1ffd16c3-25ac-4839-9ea9-4efd32926b95 · read 2026-08-30
On older people, the label states: “Of the total number of subjects in clinical studies of ziprasidone, 2.4 percent were 65 and over.”
US prescribing information · 1ffd16c3-25ac-4839-9ea9-4efd32926b95 · read 2026-08-30
On people who are pregnant, the label states: “Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including ziprasidone mesylate for injection, during pregnancy.”
US prescribing information · 1ffd16c3-25ac-4839-9ea9-4efd32926b95 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Limited data from a published case report indicate the presence of ziprasidone in human milk.”
US prescribing information · 1ffd16c3-25ac-4839-9ea9-4efd32926b95 · read 2026-08-30
On people with reduced liver function, the label states: “A half-life of 7.1 hours was observed in subjects with cirrhosis compared to 4.8 hours in the control group.”
US prescribing information · 1ffd16c3-25ac-4839-9ea9-4efd32926b95 · read 2026-08-30
On people with reduced kidney function, the label states: “Because ziprasidone is highly metabolized, with less than 1% of the drug excreted unchanged, renal impairment alone is unlikely to have a major impact on the pharmacokinetics of ziprasidone.”
US prescribing information · 1ffd16c3-25ac-4839-9ea9-4efd32926b95 · read 2026-08-30
Where the result stopped carrying
NCT00312494, the 680-patient add-on trial in acute mania, missed at p=0.1077 and p=0.4274 with the higher dose performing worse than the lower
Four out of five ziprasidone patients in CATIE stopped the drug within eighteen months
The 2001 approval came with a comparative QT disadvantage written into the Indications section itself, a position no other drug on this page occupies
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Given by a clinician
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral capsule taken twice daily with food, and an intramuscular injection for acute agitation in schizophrenia
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S6.
No source is stored against this line.
What is in the pack
The capsule must be swallowed whole with a meal and must not be opened, crushed or chewed. Fed bioavailability is about 60% and absorption roughly doubles with food, so the meal is part of the dose. The intramuscular form is a sulfobutylether-beta-cyclodextrin complex, a formulation choice forced by the free base being too poorly water-soluble to inject on its own. There is no long-acting injectable.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
The United States label carries a boxed warning for increased mortality in elderly patients with dementia-related psychosis. Section 5.3 covers QT prolongation and the risk of sudden death, and combination with other QT-prolonging drugs is a contraindication rather than a caution. Congenital long QT syndrome, a history of cardiac arrhythmias, bradycardia, hypokalaemia and hypomagnesaemia are all reasons to avoid it. Section 5.5 covers severe cutaneous adverse reactions including DRESS and Stevens-Johnson syndrome, which are sometimes fatal. Neuroleptic malignant syndrome, tardive dyskinesia, metabolic changes, orthostatic hypotension, leukopenia, neutropenia and agranulocytosis, seizures and cerebrovascular events in elderly patients with dementia are all in the label.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral capsule taken twice daily with food, and an intramuscular injection for acute agitation in schizophrenia
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
Fed bioavailability is about 60% and absorption roughly doubles with food, so the meal is part of the dose. The intramuscular form is a sulfobutylether-beta-cyclodextrin complex, a formulation choice forced by the free base being too poorly water-soluble to inject on its own. There is no long-acting injectable.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
112 products list this as an active ingredient in the United States drug directory. 112 of them contain it and nothing else.
FDA National Drug Code directory · 82449-004 · read 2026-08-29
They are sold as capsule, injection, powder, lyophilized, for solution and powder, taken intramuscular and oral.
FDA National Drug Code directory · 82449-004 · read 2026-08-29
The regulator's established pharmacologic class for it is atypical antipsychotic [epc].
FDA National Drug Code directory · 82449-004 · read 2026-08-29
40 published labels name it as an active ingredient. 40 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 1ffd16c3-25ac-4839-9ea9-4efd32926b95 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 1ffd16c3-25ac-4839-9ea9-4efd32926b95 · read 2026-08-29
Ziprasidone Mesylate is intramuscular at 3 DOSAGE FORMS AND STRENGTHS Ziprasidone mesylate for injection is available in a single-dose vial as ziprasidone mesylate (20 mg ziprasidone/mL when reconstituted according to label instructions) [see Dosage and Admini…, recorded as fda label in effect 2025-09-16 in the United States.
US prescribing information · 1ffd16c3-25ac-4839-9ea9-4efd32926b95 · read 2026-08-30
Recorded price in US: 0.26712–21.8074 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 57 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of 3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That ZODIAC showed ziprasidone does not cause dangerous arrhythmias — its authors state it was neither powered nor designed to examine rare events like torsade de pointes
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a favourable weight and metabolic profile means fewer cardiovascular events — the only mortality trial found parity with olanzapine, not superiority
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That adding ziprasidone to lithium or valproate helps in acute mania — a 680-patient trial found neither dose arm beat placebo
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That taking the capsule at a convenient time is equivalent to taking it as tested — fasted dosing roughly halves absorption
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of 3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
The label's own Indications section says other drugs should often be tried first
In plain words
Most drug labels put their warnings in the warnings section. Ziprasidone's United States label puts a sentence in the very first section, the one that says what the drug is for, telling prescribers that in many cases the conclusion would be to try something else first.
What was measured
The text of the approved United States label, section 1
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Section 1 of the United States prescribing information, immediately after listing the indications, states that the prescriber should consider the finding of ziprasidone's greater capacity to prolong the QT/QTc interval compared to several other antipsychotic drugs, that QTc prolongation is associated in some other drugs with the ability to cause torsade de pointes, and that "in many cases this would lead to the conclusion that other drugs should be tried first." Placing a comparative disadvantage inside Indications and Usage rather than in Warnings is unusual, and it is a regulatory judgement about how the drug should be positioned rather than a finding from any single trial.
Source
United States prescribing information for ziprasidone hydrochloride, section 1 (Indications and Usage), via the openFDA drug label endpoint
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Nine to fourteen milliseconds more QT than four comparator antipsychotics
In plain words
A study compared ziprasidone directly against four other antipsychotics on how much they stretch the heart's electrical recovery time. Ziprasidone added about 9 to 14 milliseconds more than all four, and about 14 milliseconds less than thioridazine, the drug that was later effectively abandoned over this issue.
What was measured
Mean change in QTc from baseline at maximum plasma concentration, against four comparator antipsychotics and thioridazine
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The head-to-head study described in section 5.3 of the United States label measured electrocardiograms at maximum plasma concentration in patient volunteers, both with each drug alone and with each drug co-administered with a CYP3A4 inhibitor. The mean increase in QTc from baseline for ziprasidone was approximately 9 to 14 msec greater than for risperidone, olanzapine, quetiapine and haloperidol, and approximately 14 msec less than for thioridazine. Ketoconazole 200 mg twice daily did not augment the effect. In placebo-controlled adult trials, oral ziprasidone increased QTc by approximately 10 msec at 160 mg daily. Electrocardiograms exceeding 500 msec occurred in 2 of 2,988 ziprasidone patients (0.06%) and 1 of 440 placebo patients (0.23%), and the label states neither ziprasidone case suggested a drug role. In the fifteen-drug network meta-analysis ziprasidone was among the less favourable drugs on QTc, in a range running from 0.10 for lurasidone to -0.90 for sertindole.
Written into the record, not signed off as a reviewed claim
The 18,154-patient safety study could not measure the event it was built to reassure about
In plain words
Pfizer randomised 18,154 patients to ziprasidone or olanzapine and counted deaths over a year. The rates were the same. The authors then wrote that the study was neither powered nor designed to detect the rare arrhythmia that the QT warning is actually about.
What was measured
That equal one-year non-suicide mortality in ZODIAC demonstrates ziprasidone does not carry an arrhythmia risk — the authors state the trial was neither powered nor designed to examine rare events like torsade de pointes
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ZODIAC, registered as NCT00418171, was an open-label randomised post-marketing large simple trial in 18,154 patients with schizophrenia across 18 countries, with 9,077 in each arm. The primary outcome, non-suicide mortality within one year of initiating treatment, was 0.91 for ziprasidone and 0.90 for olanzapine, relative risk 1.02 (95% CI 0.76 to 1.39), confirmed across secondary and sensitivity analyses. The authors' own conclusion states that the study excludes a relative risk larger than 1.39 with high probability, and then states plainly: "However, the study was neither powered nor designed to examine the risk of rare events like torsade de pointes." Torsade de pointes is the event the entire QT warning exists to prevent. A study that rules out a 39% increase in all non-suicide death has genuinely useful information in it, and it is not the same information as an absence of arrhythmia risk. Follow-up was by unblinded treating psychiatrists reporting vital status, and sudden death was a post hoc secondary analysis.
Written into the record, not signed off as a reviewed claim
Adding it to lithium or valproate in acute mania did not beat placebo
In plain words
A 680-patient trial tested ziprasidone added on top of lithium or divalproex in acute mania. Neither dose range beat placebo on the mania rating scale at three weeks.
What was measured
Least-squares mean change in Young Mania Rating Scale total score at week 3: -10.95 and -10.19 on ziprasidone against -9.47 on placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
NCT00312494, a three-week double-blind multicentre placebo-controlled study of add-on oral ziprasidone in subjects with acute mania already treated with lithium or divalproex, randomised 680 patients. Least-squares mean change from baseline in Young Mania Rating Scale total score was -10.95 in the lower ziprasidone dose arm and -10.19 in the higher one, against -9.47 on placebo, with p=0.1077 and p=0.4274 respectively against placebo. Both arms missed. The dose-response also runs backwards: the higher arm performed worse than the lower one. Ziprasidone's acute mania indication is for monotherapy, and its adjunctive bipolar indication is for maintenance rather than acute treatment, so this negative trial does not contradict the label. It does mean that the add-on question in acute mania was asked at scale and answered no.
Source
NCT00312494 — A Three-Week, Double-Blind, Multicenter, Placebo-Controlled Study Evaluating the Efficacy and Safety of Add-On Oral Ziprasidone in Subjects With Acute Mania Treated With Lithium or Divalproex, posted results
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Seventy-nine per cent of its patients stopped taking it within eighteen months
In plain words
In the largest independent trial of antipsychotics ever run in the United States, ziprasidone had the second-highest dropout rate of the five drugs tested. Four out of five people had stopped by the end.
What was measured
All-cause discontinuation of assigned treatment within 18 months, by drug arm
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
CATIE randomised 1,493 patients with chronic schizophrenia at 57 United States sites to olanzapine, perphenazine, quetiapine or risperidone, with ziprasidone added after its approval. Of the 1,432 who received at least one dose, 74% discontinued before 18 months: 64% on olanzapine, 74% on risperidone, 75% on perphenazine, 79% on ziprasidone and 82% on quetiapine. Time to discontinuation for any cause was significantly longer on olanzapine than on quetiapine (p<0.001) or risperidone (p=0.002), but the comparison against ziprasidone (p=0.028) did not meet the study's adjusted threshold. The trial was funded by the National Institute of Mental Health, not by a manufacturer, and its primary measure was whether people kept taking the drug at all, which is a different and harder question than whether a rating scale moved over six weeks.
Written into the record, not signed off as a reviewed claim
It held its own as an active control in a competitor's trial
In plain words
A rival company ran a trial of its own new drug and included ziprasidone as the yardstick. Ziprasidone beat placebo by about five points on the symptom scale and matched the drug being tested.
What was measured
Mean change from baseline in PANSS total score: -12.3 on ziprasidone against -7.1 on placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
NCT00254202, sponsored by Vanda Pharmaceuticals to evaluate iloperidone in acute exacerbation of schizophrenia, randomised 593 patients to iloperidone, ziprasidone or placebo. Mean change from baseline in PANSS total score was -12.0 on iloperidone, -12.3 on ziprasidone and -7.1 on placebo. An active-control result generated by a company with no commercial interest in the comparator is a cleaner form of evidence than a sponsor's own registration trial, and it puts ziprasidone's effect size in the same place the pooled meta-analysis does: real, and modest.
Source
NCT00254202 — Vanda Pharmaceuticals iloperidone trial with ziprasidone as active control, posted results
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
A quiet metabolic profile is measured; fewer cardiovascular events are not
In plain words
Ziprasidone genuinely does not cause the weight gain that olanzapine does. Nobody has shown that people who take it instead have fewer heart attacks or live longer, and this drug carries a cardiac warning of its own running the other way.
What was measured
That avoiding weight gain with ziprasidone reduces cardiovascular events or mortality — the one trial with a mortality endpoint found parity with olanzapine, not superiority
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the fifteen-drug network meta-analysis, standardised mean differences for weight gain ran from -0.09 for haloperidol at the favourable end to -0.74 for olanzapine at the unfavourable end, with ziprasidone toward the favourable side. Those are kilograms and laboratory values, and the argument built on them is a reduction in cardiovascular events and in the fifteen-to-twenty-year mortality gap carried by people with schizophrenia. ZODIAC is the only trial that measured a hard outcome, and what it found was equality with olanzapine on one-year non-suicide mortality, not superiority. The metabolic advantage is well measured and the outcome advantage has never been demonstrated, and in ziprasidone's case a second surrogate, the QT interval, points in the opposite direction.
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What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A dopamine D2 and serotonin 5-HT2A antagonist that causes almost no weight gain, ranked eleventh of fifteen antipsychotics on symptom reduction, prolonged the QT interval by roughly 9 to 14 milliseconds more than risperidone, olanzapine, quetiapine and haloperidol in a head-to-head study, and was then randomised against olanzapine in 18,154 patients whose one-year non-suicide mortality came out identical — a study its own authors state was never designed to detect the rare arrhythmia everyone was worried about.
Recorded evidence blocks (8)
Q2
On the 3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE label: indicated for what?
"Ziprasidone capsules are indicated for the treatment of schizophrenia, as monotherapy for the acute treatment of bipolar manic or mixed episodes, and as an adjunct to lithium or valproate for the maintenance treatment of bipolar disorder. When deciding among the alternative treatments available for the condition…": indications and usage on 3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE's label. DailyMed label · 947881af-08e6-47eb-87e3-24cc162c12bc · 2026-08-11
Q3
112 registered trials of 3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE — at which phases?
Registered studies posting no result
66 of 112
112 registered studies of 3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE: 45 phase4, 33 phase3, 15 phase2, 9 na or unstated, 6 na, 6 phase1, 1 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
safety (1), accrual/recruitment (4), funding/business (1), sponsor decision unspecified (1) and other (8): 3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"Please see Detailed Description for termination reason."; 15 of 112 registered studies
Show the evidence
Trial
NCT00257192
terminated; "Please see Detailed Description for termination reason."
NCT00265382
terminated; "Please see Detailed Description for termination reason."
NCT00288353
terminated; "unable to secure additional funding"
NCT00329108
terminated; "Please see Brief Summary for Termination Reason."
NCT00374543
terminated; "Recruitment goal could not be achieved"
NCT00645229
terminated; "Please see Detailed Description for termination reason."
9 further recorded trials
NCT00645515
terminated; "This study was terminated on November 20, 2003 because of poor recruitment. This study was not terminated due to safety/efficacy."
NCT00748566
terminated; "See Detailed Description"
NCT00786318
withdrawn; "Sponsor terminated"
NCT01113541
terminated; "See termination reason in detailed description."
NCT01844700
terminated; "very slow recruitment, no sufficient results"
NCT02075047
terminated; "Based on recent input from FDA, the pre-specified final analysis will be performed at the current enrollment using a re-estimation of the sample size."
NCT02893371
terminated; "Per PI, this study is not a clinical trial and was inadvertently entered in the system"
NCT03011645
terminated; "Lack of participants"
NCT03768726
terminated; "Pfizer has decided to perform the pre-specified final analysis at the current enrollment using a re-estimation of the sample size."
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of 3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE used Ziprasidone 80-160 mg/d — over how long?
studies of 3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE used the recorded amount. ClinicalTrials.gov · 2026-09-01
2 recorded entries; human; also "Ziprasidone 80-160 mg/d", "Ziprasidone 160 mg/d"
Show the evidence
human
NCT00403546
Ziprasidone 80-160 mg/d
NCT00403546
Ziprasidone 160 mg/d
recorded 2026-09-01 · last checked 2026-09-04
Q6
3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE's half-life is 7 hours — which schedules were studied?
7 hours, the half-life 3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE's label states: "Elimination of ziprasidone is mainly via hepatic metabolism with a mean terminal half-life of about 7 hours within the proposed clinical dose range." DailyMed label · 947881af-08e6-47eb-87e3-24cc162c12bc · 2026-08-11
tmax 6 to 8 hours; bioavailability 60 %.
Show the evidence
half lifepharmacokinetics
7 hours; Elimination of ziprasidone is mainly via hepatic metabolism with a mean terminal half-life of about 7 hours within the proposed clinical dose range.
tmaxpharmacokinetics
6 to 8 hours; Absorption: Ziprasidone is well absorbed after oral administration, reaching peak plasma concentrations in 6 to 8 hours.
bioavailabilitypharmacokinetics
60 %; The absolute bioavailability of a 20 mg dose under fed conditions is approximately 60%.
metabolismpharmacokinetics
Elimination of ziprasidone is mainly via hepatic metabolism with a mean terminal half-life of about 7 hours within the proposed clinical dose range.
recorded 2026-08-11 · last checked 2026-09-04
Q7
Which 52 trials of 3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE posted no result?
Posted no result
52 of 52 completed trials
Registrations
NCT00034801, NCT00644800, NCT00645320, NCT00649064, NCT00649844 and NCT00014001, and 46 more
Completion dates
oldest 2003-03; newest 2020-01-01
Show the evidence
Trial
NCT00034801
2003-03
NCT00644800
2004-05
NCT00645320
2004-08
NCT00649064
2004-09
NCT00649844
2004-09
NCT00014001
2004-12
14 further recorded trials
NCT00181922
2004-12
NCT01581866
2005-01
NCT01581879
2005-01
NCT00634348
2005-03
NCT00650611
2005-03
NCT00208208
2005-04
NCT00645372
2005-05
NCT00650429
2005-05
NCT00143351
2005-09
NCT00136994
2005-11
NCT00145444
2005-11
NCT01006551
2006-02
NCT00137020
2006-04
NCT00635921
2006-04
Q8
At the median, 3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE's trials enrolled 92.5 people — anything larger?
Median enrolment
92.5
Largest enrolment
1037352
Registered trials counted
112
Q9
3-(1-PIPERAZINYL)-1,2-BENZISOTHIAZOLE and CYP3A4, CYP2D6 and CYTOCHROME P450: shared by which compounds?
Less than one-third of ziprasidone metabolic clearance is mediated by cytochrome P450 catalyzed oxidation.
drug_interactions
7.2 In Vitro Studies An in vitro enzyme inhibition study utilizing human liver microsomes showed that ziprasidone had little inhibitory effect on CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, and thus would not likely interfere with the metabolism of drugs primarily metabolized by these enzymes.
drug_interactions
7.4 Pharmacokinetic Interactions Carbamazepine Carbamazepine is an inducer of CYP3A4; administration of 200 mg twice daily for 21 days resulted in a decrease of approximately 35% in the AUC of ziprasidone.
drug_interactions
Ketoconazole Ketoconazole, a potent inhibitor of CYP3A4, at a dose of 400 mg QD for 5 days, increased the AUC and C max of ziprasidone by about 35 to 40%.
drug_interactions
Other inhibitors of CYP3A4 would be expected to have similar effects.
drug_interactions
7.7 Dextromethorphan Consistent with in vitro results, a study in normal healthy volunteers showed that ziprasidone did not alter the metabolism of dextromethorphan, a CYP2D6 model substrate, to its major metabolite, dextrorphan.
2 more recorded rows
Interaction statementpharmacokinetics
Ziprasidone is unlikely to interfere with the metabolism of drugs metabolized by cytochrome P450 enzymes.
Interaction statementpharmacokinetics
In vitro studies using human liver microsomes and recombinant enzymes indicate that CYP3A4 is the major CYP contributing to the oxidative metabolism of ziprasidone.
BITP, LURASIDONE METABOLITE M1, ZIPRASIDONE HYDROCHLORIDE MONOHYDRATE IMPURITY A [EP IMPURITY], ZIPRASIDONE MESILATE TRIHYDRATE IMPURITY A [EP IMPURITY], ZIPRASIDONE RELATED COMPOUND A FREE BASE
ClinicalTrials.gov — US Government work · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 5 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
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